Biodegradable supporting device

ABSTRACT

A biodegradable in vivo supporting device is disclosed. The in vivo supporting device comprises a biodegradable metal scaffold and a biodegradable polymer coating covering at least a portion of the biodegradable metal scaffold, wherein the biodegradable polymer coating has a degradation rate that is faster than the degradation rate of the biodegradable metal scaffold.

This application is a continuation application of U.S. patentapplication Ser. No. 15/206,242, filed on Jul. 9, 2016, which is acontinuation application of U.S. patent application Ser. No. 15/015,767,filed on Feb. 4, 2016, now U.S. Pat. No. 9,408,953, which is acontinuation application of U.S. patent application Ser. No. 14/826,732,filed on Aug. 14, 2015, which is a continuation application of U.S.patent application Ser. No. 14/174,600, filed on Feb. 6, 2014, now U.S.Pat. No. 9,149,565, which is a continuation application of U.S. patentapplication Ser. No. 13/416,074, filed on Mar. 9, 2012, now U.S. Pat.No. 8,834,902. The entirety of the aforementioned application isincorporated herein by reference.

FIELD

The present application generally relates to medical devices and, inparticular, to a biodegradable in vivo supporting device.

BACKGROUND

In vivo supporting devices or barrier devices, such as stents, is aman-made “tube” or “frame” inserted into a natural passage or conduit inthe body to prevent, or counteract, a disease-induced, localized flowconstriction or flow outflow like a leak or aneurysm. Supporting devicesinclude vascular supporting devices, non-vascular supporting devices,and heart failure closure or aneurysm sealing devices. Vascularsupporting devices are designed for applications in the vascular system,such as arteries and veins. Non-vascular supporting devices are used inother body lumens such as biliary, colorectal, esophageal, ureteral andurethral tract, and upper airway. Heart failure closure devices are usedto correct defects in heart, such as atrial septal defect (ASD), patentforamen ovale (PFO) and ventricular septal defect (VSD). Aneurysmsealing devices are used to close off potentially dangerous aneurysm orpseudo aneurysm throughout the vascular and non-vascular system.

In vivo supporting devices are typically made from a rigid material,such as a metal, alloy or rigid polymeric material. The supportingdevice may be made from a biodegradable material so that there is noneed to remove the device after the correction of the underline defects.A common problem with the biodegradable supporting device, however, isthat the device may disintegrate in an uncontrolled manner and breakinto large pieces which, if entering the circulation of a body fluidsuch as blood, may interfere with the normal circulation of the bodyfluid. Therefore, there exists a need for improved in vivo supportingdevices that are biodegradable in a controlled manner.

SUMMARY

One aspect of the present invention relates to an in vivo supportingdevice. The device comprises a biodegradable metal scaffold and abiodegradable polymer coating that coats at least a portion of thebiodegradable metal scaffold. In certain embodiments, the biodegradablepolymer coating has a degradation rate that is faster than thedegradation rate of the biodegradable metal scaffold. In otherembodiments, the biodegradable polymer coating has a degradation ratethat equals to, or is slower than, the degradation rate of thebiodegradable metal scaffold.

In other embodiments, the biodegradable metal scaffold comprises analloy comprising magnesium.

In other embodiments, the biodegradable metal scaffold is made from amagnesium alloy having a magnesium content of at least 96 wt. %, amanganese content of at least 1 wt. %, and at least one metal from therare earth metal group in the amount of at least 0.5 wt. %.

In other embodiments, the biodegradable metal scaffold is made from amagnesium alloy having a magnesium content of 96-97.9 wt. %, a manganesecontent of 1.6-2 wt. %, and at least one metal from the rare earth metalgroup in the amount of 0.5-2 wt. %.

In other embodiments, the biodegradable metal scaffold is made from amagnesium alloy having a magnesium content of 97.45 wt. %, a manganesecontent of 1.8 wt. %, and a cerium content of 0.75 wt. %.

In some embodiments, the biodegradable polymer coating coats metalstruts of the biodegradable metal scaffold but does not cover openingsbetween struts. In other embodiments, the biodegradable polymer coatingcoats metal struts of the biodegradable metal scaffold and coversopenings between struts. In yet other embodiments, the in vivosupporting device comprises a biodegradable polymer coating that coatsmetal struts of the biodegradable metal scaffold but does not coveropenings between struts, and a biodegradable polymer covering thatcovers the coated metal struts and openings between the metal struts.

In related embodiments, the biodegradable polymer coating or coveringcontains a drug that is distributed uniformly throughout the coating orcovering. In another related embodiment, the drug is distributednon-uniformly throughout the coating or covering.

In other embodiments, the biodegradable polymer coating or covering hasa uniform thickness of 10 μm-200 μm (i.e., the coating/covering has thesame thickness throughout the coated/covered area). In otherembodiments, the biodegradable polymer coating or covering has athickness that varies within the range of 10 μm-200 μm (i.e., thecoating/covering has different thickness in different areas).

In other embodiments, the biodegradable metal scaffold comprises metalstruts, wherein the metal struts are covered by a biodegradable polymercoating having one or more holes that allow direct contact of the metalstrut with a body fluid when the supporting device is placed inside abody lumen.

In other embodiments, the biodegradable metal scaffold comprises metalstruts, wherein the metal struts are partially covered by thebiodegradable polymer coating.

In other embodiments, the biodegradable metal scaffold comprises metal,wherein the metal struts are covered on surfaces that would otherwise beexposed to a body lumen.

In other embodiments, the in vivo supporting device is a closure devicesuch as heart failure closure devices for atrial septal defect (ASD),patent foramen ovale (PFO) and ventricular septal defect (VSD), andclosure devices for fistula and aneurysm, and the biodegradable polymercoating covers the entire exterior surface of the biodegradable metalscaffold, including spaces between metal struts of the metal scaffold.In other embodiments, the biodegradable polymer covering that covers theentire exterior surface of the biodegradable metal scaffold, includingspaces between the metal struts.

In another embodiment, the biodegradable polymer coating is amulti-layer coating comprising an outer layer having a first degradationrate and an inner layer having a second degradation rate. In certainembodiments, the first degradation rate is faster than the seconddegradation rate. In other embodiments, the first degradation rateequals to, or is slower than, the second degradation rate.

In a related embodiment, the outer layer comprises an agent, such aspaclitaxel, and sirolimus, that prevents or reduces thepost-implantation hyperplastic response or healing. In another relatedembodiment, the outer layer comprises stem cells.

In another related embodiment, the inner layer comprises an agent, suchas paclitaxel and sirolimus that prevents or reduces thepost-implantation hyperplastic response. In another related embodiment,the inner layer comprises stem cells.

In another embodiment, the biodegradable metal scaffold constitutes lessthan 50% w/w of the in vivo supporting device.

In another embodiment, the biodegradable metal scaffold constitutes lessthan 50% w/v of the in vivo supporting device.

In another embodiment, the biodegradable metal scaffold constitutes lessthan 50% v/v of the in vivo supporting device.

In another embodiment, the biodegradable metal scaffold contributes lessthan 50% of the structure performance of the in vivo supporting device.

In another embodiment, the in vivo supporting device comprises magnesiumas a minor component.

In another embodiment, the biodegradable metal scaffold has a magnesiumcontent that is less than 50% w/w of the in vivo supporting device.

In another embodiment, the biodegradable metal scaffold has a magnesiumcontent that is less than 50% w/v of the in vivo supporting device.

In another embodiment, the biodegradable metal scaffold has a magnesiumcontent that is less than 50% v/v of the in vivo supporting device.

In another embodiment, the magnesium in the in vivo supporting devicecontributes to less than 50% of the structure performance of the in vivosupporting device.

In another embodiment, the magnesium is a minor constituent of thebiodegradable metal scaffold.

In another embodiment, the biodegradable polymer coating and/or coveringcomprises a biodegradable polymer and metal particles.

In a related embodiment, the metal particles are selected from particlesof iron, magnesium, tantalum, zinc and alloys thereof.

In another related embodiment, the metal particles are nanoparticles ofiron, magnesium, tantalum, zinc and alloys thereof.

In another embodiment, the biodegradable metal scaffold is an expandablescaffold that expands after implantation and wherein the biodegradablepolymer coating and/or covering is an elastic coating/covering thatexpands with the biodegradable metal scaffold.

In another embodiment, the biodegradable metal scaffold is an expandablescaffold that expands after implantation and wherein said biodegradablepolymer coating and/or covering is a coating/covering that formsfissures when said biodegradable metal scaffold is expands in vivo.

In another embodiment, the biodegradable polymer coating is permeable tobody fluid.

Another aspect of the present invention relates to a method forproducing a biodegradable in vivo supporting device. The methodcomprises the steps of (a) producing a biodegradable metal scaffold; (b)coating the biodegradable metal scaffold with a first biodegradablepolymer coating having a first degradable rate; and (c) coating thebiodegradable metal scaffold from step (b) with a second biodegradablepolymer coating having a second degradable rate. In certain embodiments,the second degradable rate is faster than the first degradable rate. Inother embodiments, the second degradable rate is slower than the firstdegradable rate.

In some embodiments, the second biodegradable polymer coating comprisesan agent that prevents or reduces the post-implantation hyperplasticresponse.

In some embodiments, the first and second biodegradable polymer coatingcovers only the surface of the struts of the metal scaffold but not theopenings between the struts. In other embodiments, the first and secondbiodegradable polymer coating covers the surface of the struts of themetal scaffold and the openings between the struts. In otherembodiments, the first and second biodegradable polymer coating coversonly the surface of the struts of the metal scaffold but not theopenings between the struts, and the coated scaffold is further coveredwith a covering that covers the openings between the coated struts.

In other embodiments, the first and/or second biodegradable polymercoating comprises a biodegradable polymer and metal particles. In arelated embodiment, the metal particles are selected from particles ofiron, magnesium, tantalum, zinc and alloys thereof.

In another related embodiment, the metal particles are nanoparticles ofiron, magnesium, tantalum, zinc and alloys thereof.

In other embodiments, the first and/or the second coating comprises anagent, such as paclitaxel and sirolimus, that prevents or reduces thepost-implantation hyperplastic response or healing. In anotherembodiment, the first and/or the second coating comprises stem cells.

In other embodiments, the drug is embedded into the first or the secondbiodegradable polymer coating that covers evenly throughout thebiodegradable metal scaffold including openings between struts of themetal scaffold.

BRIEF DESCRIPTION OF DRAWINGS

The present invention can be better understood by reference to thefollowing drawings, wherein like references numerals represent likeelements. The drawings are merely exemplary to illustrate certainfeatures that may be used singularly or in combination with otherfeatures and the present invention should not be limited to theembodiments shown.

FIG. 1 shows an embodiment of a stent with very thin struts.

FIGS. 2A-2B show the perspective view (FIG. 2A) and cross sectional view(FIG. 2B) of a stent strut fully covered with a biodegradable polymercoating.

FIGS. 3A-3B show the perspective top view (3A) and cross sectional view(3B) views of a stent strut with a biodegradable core covered with abiodegradable layer and a small opening on the cover.

FIGS. 4A-4C show embodiments of stent struts partially covered with abiodegradable layer. FIG. 4A shows a partially covered stent strut withexposed middle section. FIG. 4B shows a partially covered stent strutwith exposed end section. FIG. 4C shows a stent strut with multipleexposed sections.

FIGS. 5A-5F show embodiments of stent strut partially covered with abiodegradable layer. FIGS. 5A and 5B show a perspective view and across-sectional view, respectively, of a stent strut covered with abiodegradable layer on the outer surface. FIGS. 5C, 5D and 5E show aperspective view and cross-sectional views of another stent strutpartially covered with a biodegradable layer. FIG. 5F shows theperspective view of a strut with a coating that covers less than half ofthe strut outer surface.

DETAILED DESCRIPTION

The practice of the present invention will employ, unless otherwiseindicated, conventional medical devices and methods within the skill ofthe art. Such techniques are explained fully in the literature. Allpublications, patents and patent applications cited herein, whethersupra or infra, are hereby incorporated by reference in their entirety.

One aspect of the present invention relates to a biodegradable in vivosupporting device. The device contains body formed with a biodegradablemetal scaffold coated with a biodegradable polymer coating. Once placedinside a body lumen, the polymer coating is capable of covering thebiodegradable metal scaffold long enough for the device to beencapsulated in the surrounding tissue so that fragments of thebiodegradable metal scaffold would be degraded and absorbed in situ atthe treatment site.

The biodegradable in vivo supporting devices include, but are notlimited to, vascular supporting devices such as vascular stents,non-vascular supporting device such as non-vascular stents, andclosure/sealing/barrier devices such as devices used to correct defectsin heart and devices used to seal fistula and aneurysms.

In some embodiments, the biodegradable polymer coating coats metalstruts of the biodegradable metal scaffold but does not cover openingsbetween struts. In other embodiments, the biodegradable polymer coatingcoats metal struts of the biodegradable metal scaffold and coversopenings between struts. In yet other embodiments, the in vivosupporting device comprises a the biodegradable polymer coating thatcoats metal struts of the biodegradable metal scaffold but does notcover openings between struts, and a biodegradable polymer covering thatcovers the coated metal struts and openings between the metal struts.

In other embodiments, the biodegradable polymer coating or covering hasa uniform thickness of 10 μm-200 μm (i.e., the coating/covering has thesame thickness throughout the coated/covered area). In otherembodiments, the biodegradable polymer coating or covering has athickness that varies within the range of 10 μm-200 μm (i.e., thecoating/covering has different thickness in different areas).

In some embodiments, the biodegradable polymer coating or coveringcontains a drug that is distributed uniformly throughout the coating orcovering. In another related embodiment, the drug is distributednon-uniformly throughout the coating or covering.

As used herein, the term “biodegradable material” or “bioresorbablematerial” refers to a material that can be broken down by eitherchemical or physical process, upon interaction with the physiologicalenvironment at the implantation site, and erodes or dissolves within aperiod of time, typically within days, weeks or months. A biodegradableor bioresorbable material serves a temporary function in the body, suchas supporting a lumen or drug delivery, and is then degraded or brokeninto components that are metabolizable or excretable.

As used herein, the term “metal” refers to both single element metalsand alloys.

As used herein, the term “stent” refers to a device which is implantedwithin a bodily lumen to hold open the lumen or to reinforce a smallsegment of the lumen. Stents can be used for treating obstructedvessels, biliary ducts, pancreatic ducts, ureters, or other obstructedlumens, fractured canals, bones with hollow centers and/or fordelivering various drugs through controlled release to the particularlumen of interest.

As used herein, the diameter of an in vivo supporting device refers tothe width across the shaft of the device body. In one embodiment, thedevice has a uniform diameter along the length of its body. In anotherembodiment, the device has a variable diameter along the length of itsbody. In one embodiment, the device has a tubular body with a distalend, a proximal end and a middle section, wherein the diameter at thedistal end is smaller than the diameter at the proximal end. In anotherembodiment, the diameter at the proximal end is smaller than thediameter at the distal end. In yet another embodiment, the diameters atthe distal end and the proximate end are both smaller than the diameterat the middle section of the device. In another embodiment, the deviceis a stent with an elongated tubular body having a distal end, aproximal end and a middle section, and at least one channel formed on orin said body to provide fluid communication between said proximal endand said distal end.

FIG. 1 shows an embodiment of a biodegradable metal scaffold comprisingthin struts. In this embodiment, the scaffold 10 comprises a tubularbody 12 and thin struts 14. In certain embodiments, the struts 14 has athickness in the range of 10 μm to 100 μm.

In some embodiments, the struts 14 are fully covered with abiodegradable polymer coating layer. FIGS. 2A-2B show the perspectiveview (FIG. 2A) and cross sectional view (FIG. 2B) of a strut 14 having ametal core 21 fully covered with a biodegradable polymer coating 23.This coating is different from the coating used in perforationmanagement devices. The coating 23 can be of varying thickness. Themetal core 21 starts to degrade after the complete degradation of thecoating 23.

In certain embodiments, the biodegradable polymer coating 23 is a porouscoating so as to allow degradation of the inner core 21 before thecomplete degradation of the coating 23. In some other embodiments, thebiodegradable polymer coating layer 23 has one or more small holes inthe coating so as to allow degradation of the inner core 21 before thecomplete degradation of the coating 23. FIGS. 3A-3B show the perspectivetop view (3A) and cross sectional view (3B) views of a stent strut 14with a biodegradable core 21 covered with a biodegradable polymercoating 23 and a small opening 25 on the coating 23. The opening 25allows for direct contact of the inner core 21 with the body fluid andearlier degradation of the core 21.

In some other embodiment, the strut 14 comprises a metal core 21partially covered with a biodegradable polymer coating 23. FIGS. 4A-4Cshow embodiments of a strut 14 having a metal core 21 with one or morecovered sections and one or more exposed sections. In one embodiment,the metal core 21 has covered section 27, and an exposed middle section29 (FIG. 4A). In another embodiment, the metal core 21 has coveredsections 31 and an exposed end section 33 (FIG. 4B). In anotherembodiment, the metal core 21 has multiple covered sections 35 andmultiple exposed sections 37 (FIG. 4C) that allow earlier degradation ofthe device.

In some other embodiments, the metal core 21 is covered with thebiodegradable polymer coating 23 on certain sides and surfaces. In oneembodiment, the metal core 21 is covered with the biodegradable polymercoating 23 in such a manner that, when placed in a body lumen, the metalcore surfaces that face the lumen opening and are exposed to the bodyfluid in the lumen are covered with the biodegradable polymer coating 23to reduce the rate of degradation, while the metal core surfaces thatare in contact with the lumen wall are not covered. FIGS. 5A-5E showvarious embodiments of struts 14 with side-coated metal core 21. FIGS.5A and 5B show the perspective view (FIG. 5A) and cross sectional view(FIG. 5B) of struts with coatings that cover about half of the strutouter surface. FIGS. 5C-5D show the perspective view (FIG. 5C) and crosssectional views (FIGS. 5D and 5E) of a strut with a coating 23 thatcover more than half of the outer surface of the core 14. FIG. 5F, onthe other hand, shows the perspective view of struts 14 with coatingsthat cover less than half of the strut outer surface.

The Biodegradable Metal Scaffold

The metal scaffold or can be made from any biodegradable metal oralloys. Examples of such materials include, but are not limited to,lithium, sodium, magnesium, aluminum, potassium, calcium, cerium,scandium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel,copper, zinc, gallium, silicon, yttrium, zirconium, niobium, molybdenum,technetium, ruthenium, rhodium, palladium, silver, indium, tin,lanthanum, cerium, praseodymium, neodymium, promethium, samarium,europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium,ytterbium, lutetium, tantalum, tungsten, rhenium, platinum, gold, leadand alloys thereof.

In certain embodiments, the biodegradable metal scaffold is made from analloy comprising a combination of material that will decompose in thebody comparatively rapidly, typically within a period of several months,and form harmless constituents. To obtain uniform corrosion, the alloymay comprises a component, such as magnesium, titanium, zirconium,niobium, tantalum, zinc or silicon, which covers itself with aprotective oxide coat. A second component, such as lithium sodium,potassium, calcium, iron or manganese, which possesses sufficientsolubility in blood or interstitial fluid, is added to the alloy achieveuniform dissolution of the oxide coat. The corrosion rate can beregulated through the ratio of the two components.

Preferably, the alloy is to be composed so that the corrosion productsare soluble salts, such as sodium, potassium, calcium, iron or zincsalts, or that non-soluble corrosion products, such as titanium,tantalum or niobium oxide originate as colloidal particles. Thecorrosion rate is adjusted by way of the composition so that gases, suchas hydrogen which evolves during the corrosion of lithium, sodium,potassium, magnesium, calcium or zinc, dissolve physically, not formingany macroscopic gas bubbles.

The biodegradable metal scaffold may further comprise one or more metalsalts. Examples of metal salts include, but are not limited to salts ofthe following acids: sulfuric acid, sulfonic acid, phosphoric acid,nitric acid, nitrous acid, perchloric acid, hydrobromic acid,hydrochloric acid, formic acid, acetic acid, propionic acid, succinicacid, oxalic acid, gluconic acid, (glyconic acid, dextronic acid),lactic acid, malic acid, tartaric acid, tartronic acid (hydroxymalonicacid, hydroxypropanedioic acid), fumaric acid, citric acid, ascorbicacid, maleic acid, malonic acid, hydroxymaleic acid, pyruvic acid,phenylacetic acid, (o-, m-, p-) toluic acid, benzoic acid,p-aminobenzoic acid, p-hydroxybenzoic acid, salicylic acid,p-aminosalicylic acid, methanesulfonic acid, ethanesulfonic acid,hydroxyethanesulfonic acid, ethylenesulfonic acid, p-toluenesulfonicacid, naphthylsulfonic acid, naphthylaminesulfonic acid, sulfanilicacid, camphorsulfonic acid, china acid, quinic acid, o-methyl-mandelicacid, hydrogen-benzenesulfonic acid, methionine, tryptophan, lysine,arginine, picric acid (2,4,6-trinitrophenol), adipic acid,d-o-tolyltartaric acid, glutaric acid.

In some embodiments, the metal scaffold comprises a polymer mixed withparticles of iron, magnesium, tantalum, zinc, other absorbable metals,or alloys thereof to enhance characteristics of expansion and resistanceto compression. In some related embodiments, the particles arenanoparticles.

In some embodiments, the biodegradable metal scaffold is made from amagnesium alloy. In certain embodiments, the magnesium alloy has amagnesium content of at least 20%, 30%, 40%, 50%, 60%, 70%, 80% or 90%(w/w). In other embodiments, the magnesium alloy has a magnesium contentof at least 96 wt. %, a manganese content of at least 1 wt. %, and atleast one metal from the rare earth metal group in the amount of atleast 0.5 wt. %. The rare earth metal group includes lanthanum, cerium,praseodymium, neodymium, promethium, samarium, europium, gadolinium,terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium,scandium and yttrium. In another embodiment, the biodegradable metalscaffold is made from a magnesium alloy having a magnesium content of96-97.9 wt. %, a manganese content of 1.6-2 wt. %, and at least onemetal from the rare earth metal group in the amount of 0.5-2 wt. %. Inanother embodiment, the biodegradable metal scaffold is made from amagnesium alloy having a magnesium content of 97.45 wt. %, a manganesecontent of 1.8 wt. %, and a cerium content of 0.75 wt. %.

The shape, length and diameter of the in vivo supporting device areapplication dependent. Each type of the in vivo supporting device isdesigned to fit within a specific part of the anatomy. Therefore, theshape, length, and diameter of the supporting devices differ by type toaccommodate and support different sized lumens and different clinicalneeds. For example, stent typically has a tubular body. However, eachmajor stent application, such as vascular, pancreatic, ureteral, ormetacarpal canal, and other hollow bone structures, requires a differentdiameter and shape to enable placement, to remain in place afterplacement, to stabilize and support the anatomy it is placed in, and toallow conformance to the normal anatomy. Most stents bodies define anenclosed or open channel that allows a body fluid to flow though thestents in a body lumen. In certain embodiments, a stent body may furtherinclude a center lumen to accommodate a guide wire. This center lumenmay provide additionally flow throughput after the removal of guidewire.

The biodegradable metal scaffold can be expandable. In one embodiment,the biodegradable metal scaffold is of two different diametricaldimensions due to radial deformation of its elastic elements. Beforebeing positioned at the place of reconstruction, the biodegradable metalscaffold is deformed/compressed/folded so as to minimize its diametricaldimension. Then the biodegradable metal scaffold is placed, in thedeformed state, inside a transporting means by arranging it on a specialsetting bulb. Once the biodegradable metal scaffold has been transportedto the place of reconstruction, the setting bulb is expanded so that thebiodegradable metal scaffold diameter is maximized. In anotherembodiment, the biodegradable metal scaffold has a plurality of flexibleor foldable channel walls or leaflets extending from the centerrod/hub/cam. The channel walls or leaflets are kept in a folded positionduring the delivery process and are released only at the treatment site.In other embodiments, the biodegradable metal scaffold isballoon-expandable or is made from a self-expanding metal or alloy, suchas nitinol.

In certain embodiments, the biodegradable metal scaffold with thinstruts is made from iron or magnesium alloys. In one embodiment, thebiodegradable metal scaffold with thin struts is made from a magnesiumalloy having a magnesium content of at least 96 wt. %, a manganesecontent of at least 1 wt. %, and at least one metal from the rare earthmetal group in the amount of at least 0.5 wt. %. In another embodiment,the biodegradable metal scaffold is made from a magnesium alloy having amagnesium content of 96-97.9 wt. %, a manganese content of 1.6-2 wt. %,and at least one metal from the rare earth metal group in the amount of0.5-2 wt. %. In another embodiment, the biodegradable metal scaffold ismade from a magnesium alloy having a magnesium content of 97.45 wt. %, amanganese content of 1.8 wt. %, and a cerium content of 0.75 wt. %.Comparing to regular magnesium alloys that do not contain manganese, themanganese-containing magnesium alloys of the present invention havesignificantly increased mechanical strength and significantly less orslower hydrogen gas production after implantation. In other embodiments,the biodegradable metal scaffold with thin struts is made from magnesiumalloys with a high zinc content (e.g., 28 wt % or higher) to reducehydrogen production after implantation.

In certain embodiments, the biodegradable metal scaffold constitutesless than 50%, 45%, 40%, 35%, 30%, 25% or 20% by weight of thesupporting device. In other embodiments, the biodegradable metalscaffold constitutes a minor component of the supporting device. As usedherein, the term “minor component” refers to a component of thesupporting device that has a smaller weight percentage than anothercomponent of the supporting device. For example, the metal scaffold is aminor component in a device having metal content of 40 wt % and abiodegradable polymer content of 45 wt %. In some embodiments, thebiodegradable metal scaffold constitutes a minor component of thesupporting device and contributes to less than 50% of the overallmechanical strength of the supporting device.

In other embodiments, the supporting device contains magnesium as aminor component of the supporting device. In some embodiments, thesupporting device contains magnesium as a minor component at 10-30 wt %of the total device. In some embodiments, the magnesium constitutes aminor component of the supporting device and contributes to less than50% of the overall mechanical strength of the supporting device.

In certain embodiments, the biodegradable metal scaffold with thinstruts needs to be supplemented by the biodegradable polymer coating toachieve sufficient strength to support a vessel. In some embodiments,the biodegradable metal scaffold is expandable after implantation to anexpanded form having different diameters at each end of the scaffold.The biodegradable polymer coating helps the scaffold to maintain thesediameters after implantation. In other embodiments, the biodegradablemetal scaffold is made from an alloy with magnesium as a minorconstituent. As used herein, the term “minor constituent” refers to aconstituent in an alloy that has a smaller weight percentage thananother constituent in the alloy. For example, manganese is a minorconstituent in an alloy having a magnesium content of 90 wt. % and amanganese content of 10 wt. %. In some embodiments, the magnesiumconstitutes a minor constituent of the alloy and the biodegradable metalscaffold contributes to less than 50% of the overall mechanical strengthof the supporting device.

In other embodiments, the biodegradable metal scaffold constitutes lessthan 50% w/w of the in vivo supporting device.

In other embodiments, the biodegradable metal scaffold constitutes lessthan 50% w/v of the in vivo supporting device.

In other embodiments, the biodegradable metal scaffold constitutes lessthan 50% v/v of the in vivo supporting device.

In other embodiments, the biodegradable metal scaffold contributes lessthan 50% of the structure performance of the in vivo supporting device.

In other embodiments, the biodegradable metal scaffold has a magnesiumcontent that is less than 50% w/w of the in vivo supporting device.

In other embodiments, the biodegradable metal scaffold has a magnesiumcontent that is less than 50% w/v of the in vivo supporting device.

In other embodiments, the biodegradable metal scaffold has a magnesiumcontent that is less than 50% v/v of the in vivo supporting device.

In other embodiments, the magnesium in the in vivo supporting devicecontributes to less than 50% of the structure performance of the in vivosupporting device.

The Biodegradable Polymer Coating or Covering

The biodegradable polymer coating or covering comprises one or morebiodegradable polymers. Examples of biodegradable polymers include, butare not limited to, polydioxanone, polycaprolactone, polygluconate,poly(lactic acid) polyethylene oxide copolymer, modified cellulose,polyhydroxybutyrate, polyamino acids, polyphosphate ester,polyvalerolactone, poly-ε-decalactone, polylactonic acid, polyglycolicacid, polylactides, polyglycolides, copolymers of the polylactides andpolyglycolides, poly-ε-caprolactone, polyhydroxybutyric acid,polyhydroxybutyrates, polyhydroxyvalerates,polyhydroxybutyrate-co-valerate, poly(1,4-dioxane-2,3-one),poly(1,3-dioxane-2-one), poly-para-dioxanone, polyanhydrides, polymaleicacid anhydrides, polyhydroxy methacrylates, fibrin, polycyanoacrylate,polycaprolactone dimethylacrylates, poly-β-maleic acid, polycaprolactonebutyl acrylates, multiblock polymers from oligocaprolactonediols andoligodioxanonediols, polyether ester multiblock polymers from PEG andpoly(butylene terephthalates), polypivotolactones, polyglycolic acidtrimethyl carbonates, polycaprolactone glycolides, poly(γ-ethylglutamate), poly(DTH-iminocarbonate), poly(DTE-co-DT-carbonate),poly(bisphenol A-iminocarbonate), polyorthoesters, polyglycolic acidtrimethyl carbonate, polytrimethyl carbonates, polyiminocarbonates,poly(N-vinyl)-pyrrolidone, polyvinyl alcohols, polyester amides,glycolized polyesters, polyphosphoesters, polyphosphazenes,poly[p-carboxyphenoxy)propane], polyhydroxy pentanoic acid,polyanhydrides, polyethylene oxide propylene oxide, soft polyurethanes,polyurethanes having amino acid residues in the backbone,polyetheresters such as polyethylene oxide, polyalkene oxalates,polyorthoesters as well as copolymers thereof, lipids, carrageenans,fibrinogen, starch, collagen, protein based polymers, polyamino acids,synthetic polyamino acids, zein, polyhydroxyalkanoates, pectic acid,actinic acid, carboxymethyl sulfate, albumin, hyaluronic acid, chitosanand derivatives thereof, heparan sulfates and derivates thereof,heparins, chondroitin sulfate, dextran, β-cyclodextrins, copolymers withPEG and polypropylene glycol, gum arabic, guar, gelatin, collagenN-hydroxysuccinimide, lipids, phospholipids, polyacrylic acid,polyacrylates, polymethyl methacrylate, polybutyl methacrylate,polyacrylamide, polyacrylonitriles, polyamides, polyetheramides,polyethylene amine, polyimides, polycarbonates, polycarbourethanes,polyvinyl ketones, polyvinyl halogenides, polyvinylidene halogenides,polyvinyl ethers, polyisobutylenes, polyvinyl aromatics, polyvinylesters, polyvinyl pyrrolidones, polyoxymethylenes, polytetramethyleneoxide, polyethylene, polypropylene, polytetrafluoroethylene,polyurethanes, polyether urethanes, silicone polyether urethanes,silicone polyurethanes, silicone polycarbonate urethanes, polyolefinelastomers, EPDM gums, fluorosilicones, carboxymethyl chitosanspolyaryletheretherketones, polyetheretherketones, polyethyleneterephthalate, polyvalerates, carboxymethylcellulose, cellulose, rayon,rayon triacetates, cellulose nitrates, cellulose acetates, hydroxyethylcellulose, cellulose butyrates, cellulose acetate butyrates, ethyl vinylacetate copolymers, polysulfones, epoxy resins, ABS resins, EPDM gums,silicones such as polysiloxanes, polydimethylsiloxanes, polyvinylhalogens and copolymers, cellulose ethers, cellulose triacetates,chitosans and copolymers and/or mixtures of the aforementioned polymers.

In one embodiment, the biodegradable polymer coating or coveringcomprises a bioabsorable material that is degraded based on varyinglevels of pH. For example, the material may be stable at a neutral pHbut degrades at a high pH. Examples of such materials include, but arenot limited to chitin and chitosean. In another embodiment, thebioabsorable material is degradable by enzymes, such as lysozymes. Inanother embodiment, the biodegradable polymer coating materials bind tothe hydrogen atoms in the body fluid and therefore lower the local pH todelay the absorption of the biodegradable polymer coating materials(which are degraded at high pH).

In another embodiment, the biodegradable polymer coating or coveringcomprises a bioabsorable material that absorbs moisture and expands insitu at the treatment site. For example, a coating made of chitin or avariable copolymer of chitin and PLGA or chitin and magnesium and otherraw earth minerals would swell once it comes into contact with variousbody fluids. In one embodiment, the in vivo supporting device has apre-implantation diameter D_(pre) (i.e., dry diameter) and is expandableto a post-implantation diameter D_(post), (i.e., wet diameter) afterexposure to body liquid in a lumen. As used hereinafter, the“pre-implantation diameter D_(pre)” refers to the largest diameter of adevice body before implantation and the “post-implantation diameterD_(post)” refers to the largest diameter of the device body afterimplantation.

In certain embodiments, the biodegradable polymer coating or covering isformulated to have a degradable rate that is faster than the degradablerate of the metal scaffold. In other words, the biodegradable polymercoating would dissolve more rapidly than the metal scaffold afterimplantation. Preferably, the biodegradable polymer coating or coveringwill cover the entire biodegradable metal scaffold long enough for thedevice to be fully encapsulated in the tissue so that the metal scaffoldis degraded while encapsulated in the tissue, thus avoiding thepossibility of releasing metal fragments into a body lumen duringdegradation. In certain embodiments, the metal scaffold is coated with abiodegradable polymer coating that degrades in one, two, three or fourweeks after implantation.

In some other embodiments, the biodegradable polymer coating or coveringis mixed with, embedded with, or configured to carry, various agents orcells. Examples of agents that can be mixed with, embedded into orcarried by the biodegradable polymer coating include, but are notlimited to, small molecule drugs, biologicals and gene transfer vectors.

Examples of small molecule drugs include, but are not limited to,sirolumus, rapamycian, and other antiproliferating agent.

Examples of biologicals include, but are not limited to, antimicrobialagents and chemotherapeutic agents.

The term “antimicrobial agent” as used in the present invention meansantibiotics, antiseptics, disinfectants and other synthetic moieties,and combinations thereof, that are soluble in organic solvents such asalcohols, ketones, ethers, aldehydes, acetonitrile, acetic acid, formicacid, methylene chloride and chloroform. Classes of antibiotics that canpossibly be used include tetracyclines (i.e., minocycline), rifamycins(i.e., rifampin), macrolides (i.e., erythromycin), penicillins (i.e.,nafcillin), cephalosporins (i.e., cefazolin), other β-lactam antibiotics(imipenem, aztreonam), aminoglycosides (i.e., gentamicin),chloramphenicol, sulfonamides (i.e., sulfamethoxazole), glycopeptides(i.e., vancomycm), quinolones (i.e., ciprofloxacin), fusidic acid,trimethoprim, metronidazole, clindamycin, mupirocin, polyenes (i.e.,amphotericin B), azoles (i.e., fluconazole) and β-lactam inhibitors(i.e., sulbactam).

Examples of specific antibiotics that can be used include minocycline,rifampin, erythromycin, nafcillin, cefazolin, imipenem, aztreonam,gentamicin, sulfamethoxazole, vancomycin, ciprofloxacin, trimethoprim,metronidazole, clindamycin, teicoplanin, mupirocin, azithromycin,clarithromycin, ofloxacin, lomefloxacin, norfloxacin, nalidixic acid,sparfloxacin, pefloxacin, amifloxacin, enoxacin, fleroxacin,temafloxacin, tosufloxacin, clinafloxacin, sulbactam, clavulanic acid,amphotericin B, fluconazole, itraconazole, ketoconazole and nystatin.Other examples of antibiotics, such as those listed in U.S. Pat. No.4,642,104, herein incorporated by reference, will readily suggestthemselves to those of ordinary skill in the art. Examples ofantiseptics and disinfectants are thymol, a-terpineol,methylisothiazolone, cetylpyridinium, chloroxylenol, hexachlorophene,cationic biguanides (i.e., chlorhexidine, cyclohexidine),methylenechloride, iodine and iodophores (i.e., povidone-iodine),triclosan, furanmedical preparations (i.e., nitrofurantoin,nitrofurazone), methenamine, aldehydes (i.e., glutaraldehyde,formaldehyde) and alcohols. Other examples of antiseptics anddisinfectants will readily suggest themselves to those of ordinary skillin the art.

Chemotherapeutic agents can be mixed with the biodegradable polymercoating in a manner analogous to that of antimicrobial agents. Exemplarychemotherapeutic agents include but are not limited to cis-platinum,paclitaxol, 5-flourouracial, gemcytobine and navelbine. Thechemotherapeutic agents are generally grouped as DNA-interactive agents,antimetabolites, tubulin-interactive agents, hormonal agents,hormone-related agents, and others such as asparaginase or hydroxyurea.Each of the groups of chemotherapeutic agents can be further divided bytype of activity or compound. The chemotherapeutic agents used incombination with the anti-cancer agents or benzimidazoles of thisinvention include members of all of these groups. For a detaileddiscussion of the chemotherapeutic agents and their method ofadministration, see Dorr, et al, Cancer Chemotherapy Handbook, 2dedition, pages 15-34, Appleton & Lange (Connecticut, 1994), hereinincorporated by reference.

Examples of DNA-interactive agents include, but are not limited to,alkylating agents, DNA strand-breakage agents; intercalating andnonintercalating topoisomerase II inhibitors, and DNA minor groovebinders. Alkylating agents generally react with a nucleophilic atom in acellular constituent, such as an amino, carboxyl, phosphate, orsulfhydryl group in nucleic acids, proteins, amino acids, orglutathione. Examples of alkylating agents include, but are not limitedto, nitrogen mustards, such as chlorambucil, cyclophosphamide,isofamide, mechlorethamine, melphalan, uracil mustard; aziridines, suchas thiotepa; methanesulfonate esters such as busulfan; nitroso, ureas,such as cannustine, lomustine, streptozocin; platinum complexes, such ascisplatin, carboplatin; bioreductive alkylator, such as mitomycin, andprocarbazine, dacarbazine and altretamine. DNA strand breaking agentsinclude, but are not limited to, bleomycin. Intercalating DNAtopoisomerase II inhibitors include, but are not limited to,intercalators such as amsacrine, dactinomycin, daunorubicin,doxorubicin, idarubicin, and mitoxantrone.

Nonintercalating DNA topoisomerase II inhibitors include, but are notlimited to etoposide and teniposide. DNA minor groove binders include,but are not limited to, plicamycin.

Antimetabolites interfere with the production of nucleic acids by one orthe other of two major mechanisms. Some of the drugs inhibit productionof the deoxyribonucleoside triphosphates that are immediate precursorsfor DNA synthesis, thus inhibiting DNA replication. Some of thecompounds, for example, purines or pyrimidines, are sufficient to beable to substitute for them in the anabolic nucleotide pathways. Theseanalogs can then be substituted into the DNA and RNA instead of theirnormal counterparts. The antimetabolites useful herein include: folateantagonists such as methotrexate and trimetrexate pyrimidineantagonists, such as fluorouracil, fluorodeoxyunridine, CB3717,azacytidine, cytarabine, and floxuridine purine antagonists includemercaptopurine, 6-thioguanine, fludarabine, pentostatin; sugar modifiedanalogs include cyctrabine, fludarabine; ribonucleotide reductaseinhibitors include hydroxyurea. Tubulin interactive agents act bybinding to specific sites on tubulin, a protein that polymerizes to formcellular microtubules. Microtubules are critical cell structure units.When the interactive agents bind on the protein, the cell cannot formmicrotubules tubulin interactive agents including vincristine andvinblastine, both alkaloids and paclitaxel.

Hormonal agents are also useful in the treatment of cancers and tumors.They are used in hormonally susceptible tumors and are usually derivedfrom natural sources. These include: estrogens, conjugated estrogens andethinyl estradiol and diethylstilbestrol, chlorotrianisene andidenestrol; progestins such as hydroxyprogesterone caproate,medroxyprogesterone, and megestrol; androgens such as testosterone,testosterone propionate; fluoxymesterone, methyltestosterone; adrenalcorticosteroids are derived from natural adrenal cortisol orhydrocortisone. They are used because of their anti-inflammatorybenefits as well as the ability of some to inhibit mitotic divisions andto halt DNA synthesis. These compounds include prednisone,dexamethasone, methylprednisolone, and prednisolone.

Hormone-related agents include, but are not limited to, leutinizinghormone releasing hormone agents, gonadotropin-releasing hormoneantagonists and anti-hormonal agents. Gonadotropin-releasing hormoneantagonists include leuprolide acetate and goserelin acetate. Theyprevent the biosynthesis of steroids in the testes and are usedprimarily for the treatment of prostate cancer.

Antihormonal agents include antiestrogenic agents such as tamosifen,antiandrogen agents such as flutamide; and antiadrenal agents such asmitotane and amminoglutethimide. Hydroxyurea appears to act primarilythrough inhibition of the enzyme ribonucleotide reductase. Asparaginaseis an enzyme that converts asparagine to nonfunctional aspartic acid andthus blocks protein synthesis in the tumor.

Gene transfer vectors are capable of introducing a polynucleotide into acell. The polynucleotide may contain the coding sequence of a protein ora peptide, or a nucleotide sequence that encodes a iRNA or antisenseRNA. Examples of gene transfer vectors include, but are not limited to,non-viral vectors and viral vectors. Non-viral vectors typically includea plasmid having a circular double stranded DNA into which additionalDNA segments can be introduced. The non-viral vector may be in the formof naked DNA, polycationic condensed DNA linked or unlinked toinactivated virus, ligand linked DNA, and liposome-DNA conjugates. Viralvectors include, but are not limited to, retrovirus, adenovirus,adeno-associated virus (AAV), herpesvirus, and alphavirus vectors. Theviral vectors can also be astrovirus, coronavirus, orthomyxovirus,papovavirus, paramyxovirus, parvovirus, picornavirus, poxvirus, ortogavirus vectors.

The non-viral and viral vectors also include one or more regulatorysequences operably linked to the polynucleotide being expressed. Anucleotide sequence is “operably linked” to another nucleotide sequenceif the two sequences are placed into a functional relationship. Forexample, a coding sequence is operably linked to a 5′ regulatorysequence if the 5′ regulatory sequence can initiate transcription of thecoding sequence in an in vitro transcription/translation system or in ahost cell. “Operably linked” does not require that the DNA sequencesbeing linked are contiguous to each other. Intervening sequences mayexist between two operably linked sequences.

In one embodiment, the gene transfer vector encodes a short interferingRNA (siRNA). siRNAs are dsRNAs having 19-25 nucleotides. siRNAs can beproduced endogenously by degradation of longer dsRNA molecules by anRNase III-related nuclease called Dicer. siRNAs can also be introducedinto a cell exogenously or by transcription of an expression construct.Once formed, the siRNAs assemble with protein components intoendoribonuclease-containing complexes known as RNA-induced silencingcomplexes (RISCs). An ATP-generated unwinding of the siRNA activates theRISCs, which in turn target the complementary mRNA transcript byWatson-Crick base-pairing, thereby cleaving and destroying the mRNA.Cleavage of the mRNA takes place near the middle of the region bound bythe siRNA strand. This sequence specific mRNA degradation results ingene silencing. In another embodiment, the gene transfer vector encodesan antisense RNA.

Examples of cells include, but are not limited to, stem cells or otherharvested cells.

In certain embodiments, the biodegradable polymer coating or covering isa multi-layer coating comprising a fast degrading layer and a slowdegrading layer. In some embodiments, the fast degrading layer is anouter layer and the slow degrading layer is an inner layer. In someother embodiments, the fast degrading layer is an inner layer and theslow degrading layer is an outer layer.

In some embodiments, the fast degrading layer further comprises an agentthat prevents or reduces the post-implantation hyperplastic response.Examples of such an agent include, but are not limited to, paclitaxeland sirolimus. The slow degrading layer may contain the same agent or adifferent agent, such as the small molecule drugs, biologicals or genetransfer vectors described above. In one embodiment, the fast degradinglayer is an inner layer having embedded therein a drug or stem cells.When the slow degrading outer layer is degraded, the fast degradinginner layer quickly releases the drug or cells.

In other embodiments, the fast degrading layer is an outer layercomprising fissures so that body fluid may contact the slow degradinginner layer before the degradation of the outer layer. In the case of anexpandable in vivo supporting device, the coating can be made of anelastic polymer composition to allow expansion of the biodegradablemetal scaffold while maintaining the integrity of the coating. Inanother embodiment, the coating a made of a brittle composition thatwould form fissures when the metal scaffold expands so as to allowsimultaneous degradation of both the coating and the metal scaffold. Therequired elasticity may be achieved using a mixture of crystalline andamorphous polymers, or co-polymers containing both amorphous segmentsand crystalline segments. For example, poly-D-lactide is amorphous andelastic, while poly-L-lactide has a higher level of crystallinity and ismore brittle. A copolymer made of D- and L-lactide would be have anelasticity somewhere in between poly-D-lactide and poly-L-lactide.

In another embodiment, the biodegradable polymer coating or covering ispermeable to body fluid to allow simultaneous degradation of both thecoating and the metal scaffold after implantation. The permeability ofthe biodegradable polymer coating or covering may be created by using aporous polymer coating/covering or by creating fissures or holes in thepolymer coating/covering during the manufacturing process.

In certain embodiments, the fast degrading outer layer is degradablewithin 1, 2, 3, 4, 5, 6 or 7 days and the slow degrading inner layer isdegradable within 1, 2, 3 and 4 weeks.

The thickness of the outer and inner layers may be adjusted to achievethe desired degradation behavior. In certain embodiments, the thicknessof each layer is in the range of 10 μm to 100 μm. In devices with ametal scaffold having very thin struts, the total thickness of the outerand inner coating layers is in the range of 10 μm to 100 μm. In someembodiments, the outer and/or inner coating layer has an uneventhickness.

In some embodiments, the biodegradable polymer coating or coveringcomprises materials, such as metal particles, that assist with theillumination of the in vivo supporting device under fluoroscopy. Suchmaterials could also be used to help support the material structure ofthe polymer coating. In some embodiments, the biodegradable polymercoating comprises polymer material mixed with iron or magnesiumnanoparticles to help support the polymer material.

In other embodiments, the in vivo supporting device comprises an elasticpolymer coating so that it can be used in non-conforming lesions. Insome embodiments, the elastic polymer is mixed with metal particles thatallow the material to be more malleable to be crimped on the stent andto stay at its dilated from. Examples of such metal particles include,but are not limited to, particles of iron, magnesium, tantalum, zinc andalloys thereof. The metal particles can be of varying sizes and shapes.In certain embodiments, the metal particles are nanoparticles. Thecoating would have different linked structure and arrangement aftercrimping or expansion to keep the device compressed or open.

In some embodiment, the biodegradable in vivo supporting devices areclosure devices, such as heart failure closure devices for atrial septaldefect (ASD), patent foramen ovale (PFO) and ventricular septal defect(VSD), fistula closure devices for fistula and closure devices foraneurysm. In some embodiments, the coating or covering is applied viaelectro spinning or dip coating.

Manufacture of the In Vivo Supporting Device

The biodegradable metal scaffold of the in vivo supporting device can belaser cut, water jet cut, stamped, molded, laythed or formed with othermethods commonly used in the art. In one embodiment, the scaffold is cutfrom a single metal tube. The tube may be hollow or the center may becored out at varying diameters suitable for the particular indication.The scaffold is then etched and is formed on a suitable shaping deviceto give the scaffold the desired external geometry. The formed scaffoldis then coated with the biodegradable polymer coating using methods wellknown in the art. In one embodiment, the scaffold is first coated with aslow degrading inner coating and then coated with a fast degrading outercoating.

In certain embodiments, the in vivo supporting device of the presentinvention are formed in such a way as to allow fluid flow to change inthe pitch of the flow to improve flow dynamics and to speed the flow offluids throughout the device. From a tight radial design to a morelongitudinal design.

In one embodiment, spiral surface channels with large cross-sectionareas are formed to accommodate large volumes of body fluid. In anotherembodiment, multiple channels with small cross-section area are formedto accommodate large volumes of body fluid. In another embodiment, thedevice body contains a large center lumen to allow for fluid flow and aplurality of small cross-section area channels on the surface tostabilize the device in vivo.

In another embodiment, the lips of the channel walls are taped toincrease the surface area for fluid flow and grip. Changes in the depthof the pitch of the channels will also have an impact on fluid flow andstability.

In one embodiment, the metal scaffold is formed on a shaping tool thathas substantially the desired contour of the external stent dimensions.In the event the device is to be shaped to the dimensions of aparticular lumen, optical photography and/or optical videography of thetarget lumen may be conducted prior to stent formation. The geometry ofcorresponding zones and connector regions of the metal scaffold then canbe etched and formed in accordance with the requirements of that targetlumen. For example, if the topography of the biliary duct of aparticular patient is captured optically and the appropriate dimensionprovided, a patient specific in vivo supporting device can beengineered. These techniques can be adapted to other non-vascular lumensbut is very well suited for vascular applications where patient specifictopography is a function of a variety of factors such as genetics,lifestyle, etc.

The in vivo supporting device of the present invention can take on aninfinite number of characteristic combinations as zones and segmentswithin a zone can be modified by changing angles, segment lengths,segment thicknesses, pitch during the etching and forming stages ofdevice engineering or during post formation processing and polishingsteps. Moreover, by modifying the geometry, depth, and diameter of thechannels between zones, additional functionality may be achieved such asflexibility, increased fluid transport, and changes in friction.

The in vivo supporting device of the present invention may be implantedwith procedures well known to a person of ordinary skill in the art.Examples of such procedures include, but are not limited to, standardpercutaneous approach using a guide wire, endoscopic retrogradecholangiopancreatography (ERCP) placement procedures, and otherradiographic/angiographic procedures.

The above description is for the purpose of teaching the person ofordinary skill in the art how to practice the present invention, and itis not intended to detail all those obvious modifications and variationsof it which will become apparent to the skilled worker upon reading thedescription. It is intended, however, that all such obviousmodifications and variations be included within the scope of the presentinvention, which is defined by the following claims. The claims areintended to cover the claimed components and steps in any sequence whichis effective to meet the objectives there intended, unless the contextspecifically indicates the contrary.

1-30. (canceled)
 31. An in vivo supporting device, comprising: abiodegradable metal scaffold comprising metal struts; and abiodegradable polymer coating covering at least a portion of thebiodegradable metal scaffold, wherein said biodegradable polymer coatinghas a thickness of 10-200 μm and a degradation rate that is differentthan the degradation rate of the biodegradable metal scaffold, whereinthe biodegradable metal scaffold comprises an alloy, wherein the alloycomprises magnesium, manganese, and at least one rare earth metal. 32.The in vivo supporting device of claim 31, wherein the alloy has amagnesium content of 96-97.9 wt. %, a manganese content of 1.6-2 wt. %,and at least one rare earth metal in the amount of 0.5-2 wt. %.
 33. Thein vivo supporting device of claim 31, wherein the metal struts arefully covered by the biodegradable coating.
 34. The in vivo supportingdevice of claim 31, wherein the metal struts are covered by thebiodegradable polymer coating, wherein the biodegradable polymer coatinghas one or more holes that allow direct contact of the metal struts witha body fluid when the supporting device is placed inside a body lumen.35. The in vivo supporting device of claim 31, further comprising abiodegradable polymer covering that covers the exterior surface of themetal scaffold, including openings between the metal struts.
 36. The invivo supporting device of claim 35, wherein the biodegradable polymercovering comprises an agent that prevents or reduces thepost-implantation hyperplastic response.
 37. The in vivo supportingdevice of claim 31, wherein the biodegradable polymer covering comprisesa first agent that prevents or reduces post-implantation hyperplasticresponse.
 38. The in vivo supporting device of claim 37, wherein thebiodegradable polymer coating comprises a second agent that prevents orreduces post-implantation hyperplastic response.
 39. The in vivosupporting device of claim 31, wherein the biodegradable metal scaffoldis a self-expandable scaffold that expands after implantation.
 40. Thein vivo supporting device of claim 31, wherein said biodegradablepolymer coating is permeable to body fluid.
 41. The in vivo supportingdevice of claim 31, wherein said biodegradable metal scaffoldconstitutes less than 50 wt % of said supporting device.
 42. The in vivosupporting device of claim 31, wherein the rare earth metal isneodymium.
 43. The in vivo supporting device of claim 31, wherein thebiodegradable polymer coating comprises copolymers of polylactides andpolyglycolides.